Cellular Aberration

Characteristics of Normal Cells

Uniform size and shape

Each containing a nucleus of uniform size
Multiplication takes place by an orderly process in response to trauma or inflammation
Contact inhibition- recognize the presence of other cells near them
Adhere closely together (Cohesiveness)- *[Fibromectin- maintains the cohesiveness
between cells]
Cell birth is equal to death
Cell replication through the cell cycle
The process of cellular differentiation causes the cells to resemble their normal forebears
and have fully mature, specialized fxn and morphology

Cell Cycle

G1- (4hrs)- Protein & RNA synthesis

S (Synthesis) Phase (Approx. 10 hrs) DNA synthesis & duplication of chromosomes
[Interphase]
G2 (Second gap phase)- (Approx. 4 hrs)
Mitosis- Prophase > Metaphase > Anaphase > Telophase

Mitosi
s

G1

G2

S
phas
e

Cellular Fxns

Transport of metabolites
Metabolism
o Anabolism
o Catabolism

Cellular Aberration
Movement
Conduction- transmission of a stimulus from 1 part of the body to another
Absorption- mvt of a substance thru a cell membrane
Body protection- those of epithelial cells, WBC
Reproduction

Cell Adaptation

Adaptation to sublethal injury is common and part of many physiologic and disease
processes
Adaptive processes of the cell
o Hypertrophy- enlargement of cells without cel division
Ex.: Pregnant uterus enlarges fro hormonal stimulation
o Hyperplasia inc in number of cells
Reversible when stimulus is removed
o Atrophy- decrease in size of the tissue or organ / dec number/ size of indiv. Cells
Result of desease
Lack of blood supply
Aging process
Inactivity
Nutritional deficiency
o Metaplasia- transformation of one cell type to another (temporary)
Monocytes to macrophages
Normal pseudostratified columnar epithelium of the bronchi changes to
squamous epith in response to cigarette smoking

Abnormal Adaptation
o
o

Dysplasia- Abnormal differentiation of dividing cells resulting to changes in the size,

shape and organization of calls
Anaplasia- cell differentiation to a more immature or embryonic form
Like malignant tumors

Causes of lethal Injury

Physical agents
o Heat- denaturation of protein acceleration of metabolic rxns
o Cold- decreased blood flow from vasoconstriction; slowed metabolic rxns.
Thrombosis of blood vessels, freezing of cell content
o Radiation- alteration of cell structure and activity, enzyme systems; mutations
o Electrothermal injury- interruption of neural conduction, fibrillation of cardiac muscle
coaulative necrosis of skin
o Mechanical
Chemical- alteration of cell metabolism and normal enzymatic axn
Microbial
o Viruses- taking over of cell metabolism and synthesis new particles. Ex: Human
papilloma virus, Epstein-Barr Virus, Hepatitis B & C virus
o Bacteria- destruction of cell membrane or cell nucleus, production of lethal toxins.
Ex: H-pylori
Ischemic- compromised cell metabolism, acute or gradual cell death

Cellular Aberration
Immunologic
o Antigen-antibody response cause release of substances (Histamine, complement)
o Autoimmune activation of complement, w/c destroys normal cells and produces
inflammation
Neoplastic growth- cell destruction from abnormal and uncontrolled growth
Normal substances ( digestive enzymes, uric acid)- release into abdominal cavity causing
peritonitis, crystallization of excess accumulation in joints and renal tissue
Genetic disorders
Psychogenic Factors- ex. Stress

Prevention of Cancer

Primary prevention- reducing the risks of cancer in healthy people

Secondary prevention- detection and screening for early diagnosis and prompt
intervention

Cellular Aberration

CANCER

Group of diseases in which cells multiply without restraint (*no regulation of cell birth) (*no
cell death= cell birth), destroy healthy tissues (*they deprive other cells with nutrients)
and endanger life
The process that begins when abnormal cell is transformed by the genetic mutation of the
cellular DNA

Seven warning signs of cancer

C change in bowel/bladder

A a sore that does not heal

U unusual bleeding/discharge

T thickening or a lump in the breast or elsewhere

I indigestion or difficulty in swallowing

O obvious change in wart or mole

N nagging cough or hoarseness

U unexplained anemia

S sudden weight loss

Etiology
The role of oncogenes
o
o
o

Specific genes capable of triggering cancer cell growth

Produce proteins that accelerate cells rate of multiplication, increased
responsiveness to growth hormones, enable to invade other tissues
Proto-oncogenes: genes normally present in the cell
Can transform to a malignant state when activated radiation, chemicals or
viruses
Act as a on switch for cellular growth
Suppressor genes turn off or regulate unneeded cellular proliferation
Once mutated or lose their regulatory capabilities, malignant cells are
allowed to reproduce
p53 is frequently mutated in many human cancers

Genetic Factors

Deranged genes passed thru either autosomal recessive or autosomal dominant

transmission
o Recessive when both parents have abnormal genes
o Dominant when only one parent have abnormal gene
General characteristics of hereditary CA

Cellular Aberration
o Early age onset
o Marked incidence of bilateral cancer in paired organs
o Greater frequency of developing the same cancer
o Appearance in two or more member in one generation
Leukemia with chromosomal alterations
o Chronic myelogenous leukemia (CML)- Associated with Philadelphia
chromosome 22 translocation
o Acute Myelogenous leukemia (AML)- associated with trisomy 21 found in
downs syndrome
o ***

Hormonal Influence in Carcinogenesis

Making target tissues susceptible to carcinogens

Allowing cancer process to progress
Conditioning effect on the tumor
Hormones can restraint or enhance tumor growth

Precancerous lesions

Have tendency toward a malignant change

Polyps of the colon and rectum, pigmented moles, dysplasia of cervical epithelium
Pagets disease of the bone, senile keratosis, leukoplakias of oral mucosa (*leukoplakiausually present in patients with HIV/AIDS)

Chronic Irritation

Believed to be a causative factors of cancer

Coal tar products known to contain carcinogens
Belts, girdles, brassier, shirt collars
Rough jagged teeth
Scalding hot or freezing cold liquids
Indiscriminate use of laxatives

Immunologic Factors

Failure of the immune mechanism may predispose a person to certain cancers

***B-cells- responsible for tumor-surveillance (cell-mediated immune response)

Some tumors arise in areas poorly served by the immune system like the CNS
Some tumors do not stimulate antibody formation since they are similar to normal cells
Control system may become overactive and suppress the immune system
Tumor mass grows at a faster rate than the normal immunologic response can handle
o 10 million cancer cells at a time can be detected
o At least 1 cm size can be detected by conventional diagnostic methods
o Tumor of 1 cm diameter contains more than 1 billion malignant cells

Drugs that maybe oncogenic to human beings

Cytotoxic agents

Cellular Aberration

Immunosuppressive agents
Estrogens
Oral contraceptives
Androgenic anabolic steroids
Phenacetin containing analgesics

Ionizing Radiation

Electromagnetic waves or material particles with sufficient energy to ionize atoms or

molecules thereby alter their chemical behavior
Results in the breakage of either a single or double strand of the DNA helix

Sun Exposure

Ultraviolet radiation
Depletion of ozone layer
Light complexioned individuals are most susceptible

Radon and electromagnetic Fields

Radon- an inert gas that emanates from the ground and stone building materials from the
decay of uranium
EMF exposure from household app, electrical wiring, or living near electrical power lines
o The nearer one is to the source (within 50 cm), the greater the exposure
o Cellular phones are studied as the source

Air pollution

Depletion of ozone layer

Risk of lung or skin cancer

Chemical pollutants

Nitrates as food additives

Aflatoxin 13 from common molds on peanuts, soybeans, fruits, meats, cheeses
Cyclamates used a sugar substitute
Some hair dyes

Smoking and tobacco use

Smokers of 2 or more packs/day have lung cancer mortality rate 12-25 times greater than
that of a non-smoker
Connected with oral, esophageal, bladder cancer
Smoking cessation after a habit of 30 years, incidence of lung cancer decreases
Environmental tobacco smoke (ETS) exposes non-smoker to the same carcinogens as the
smoker

Nutrition

High fat, high caloric diet associated with increased risk for colon, breast, prostate,
pancreatic and endometrial cancer
Alcohol consumption and nutritional deficiencies may enhance carcinogenesis by
increasing metabolic activity of specific tobacco carcinogens

Cellular Aberration

Sexual Practices

Higher incidence of uterine cervix carcinoma those who have first coitus at an early age,
early first marriage, multiple sex partners
Carcinoma of penis virtually unknown among circumcised men
First child before age 20 have only 1/3 the risk of women older than 35 who deliver a first
child

Viruses

Viruses are thought to incorporate themselves in the genetic structure of the cells
Cervical CA may result from a virus (Human Papilloma Virus)
o Herpes like viruses (Epstein-Barr) have seen in Burkitts tumor and Hodgskins ds
cells
Hep B is more common than Hep C

Psychosocial Factors

Stressors such as life changes, loss of significant other, personality variables have been
suggested as etiologic factors
Cancer prone personality suggested but unproven
Minimal social support may be a risk factor

MULTI-STEP OF CARCINOGENESIS

Initiation
Promotion
Progression

Initiation

Begins with exposure of normal cells to carcinogens

o Carcinogens are substances that can cause cancer
o Escape normal enzymatic mechanisms and alter the genetic structure of the cellular
DNA
Normally, alterations are reversed by DNA repair mechanism or the changes initiate
programmed cellular death (apoptosis).

Promotion

Lasts for many years

Promoting factor include cigarette smoking, alcohol use, and dietary components that act
repeatedly over time on the already transformed cell
Promoters enhance the structural changes within the cell
Latent period- the period of time ranging from 1 to 40 years that elapses between the
initial genetic alteration and the actual evidence of cancer

Progression

The uncontrolled growth of a malignant tumor capable of metastasis

Tumor cells compete with normal cells and tissue for blood supply
As tumor cells grow, they stimulate vascularization (angiogenesis)
Rate of growth is referred to as doubling time- time required for tumor mass to double.

Cellular Aberration

Factors that affect tumor growth

Cell cycle time- the rate of replication of proliferating cells

Growth fraction- proportion of total cell population actively proliferating
Rate of cell loss from cell death and exfoliation of cells from tumor surface

Metastasis

Affinity for a particular tissue or organ

Lungs, brain, bone, and liver are the common sites of metastasis
Vascular, lymphatic spread (**lymphadenopathy- swollen lymph nodes)
Implantation- cells become embedded along serosal surfaces of body organs

Stages of metastasis
Stage 1
Stage 2
Stage 3

Benign
Well-differentiated
Encapsulated, grow by expansion
Slow growth
Does not spread by metastasis
No generalized effects
Does not usually cause tissue
damage
Does not usually cause death

Malignant
Undifferentiated
Infiltrates and destroy surrounding
tissues
More anaplastic, faster growth
Metastasize
Generalized effects
Extensive tissue damage
Usually causes death unless
growth is controlled

Classification by tissue of origin

Adeno epithelial tissues

Chondro- cartilage
Fibro- Fibrous connective
Glio
Hemangio
Hepato
Leiomyo- smooth muscle
Lipo
Lympho
Neuro
Meningio
osteo

Most common benign neoplasms

Fibrosarcoma- may grow anywhere but frequently grow in the uterus

Lipomas
Leiomyoma

Cellular Aberration

Malignant neoplasms

Carcinoma
Sarcoma
Carcinoma in situ- confined in the site of origin but can become invasive, eroding
surrounding tissues
Fibrosarcoma-may originate as benign
Bronchogenic carcinoma- acct s for 90% of cancers

Consequences of Cancer

Impaired immune and hematopoietic function:

o Anemia
o Thrombocytopenia (*20,000/ cumm critical level of platelet count)
o Leukopenia
Anemia + Thrombocytopenia+ Leukopenia =PANCYTOPENIA
**maybe caused by the cancer itself or by the cancer treatment

Altered Gastrointestinal function:

o Obstruction, or compression
o Increase metabolic rate and increase need for protein, carbohydrate and fats
o Anorexia (*loss of appetite)
o Cachexia- extreme body wasting and malnutrition

Motor and sensory deficits

o Related to invasion of the bone, brain, or compress nerves
o Pain

Decreased respiratory function:

o Airway obstruction
o Decreased lung capacity
o Pulmonary edema and dyspnea r/t obstruction of blood flow, lymphatic drainage
o Decreased gas exchange r/t thickening of alveolar membrane and damage of
pulmonary blood vessels

Nurses Role in the Diagnosis of CA

Explanation of the tests to be performed, sensations likely to be experienced, patients

role in the test
Encourages patient and family to express fears about test results
Supports patient and family throughout the test period
Reinforces and clarifies information

Diagnosis of Cancer

History
o Blood relatives
o Work history
o Environmental exposure

Cellular Aberration
o

Previous knowledge and perceptions about cancer

Assess clinical manifestations

o Pressure on surrounding organs or nerves
o Distortion of surrounding tissue
***Presence of lump in the breast, document using the clock position- ex. 1
cm in diameter lump present @ 9 oclock position
o Obstruction of lumen of blood vessels, intestines, ureters etc.
o Interference with organ function
o Disturbance of body metabolism

Assess
o Parasitic use of bodys nutritional needs
***S&S: Body weight loss, pallor, fatigue
o Mobilization of the bodys defensive response
***Leukocytosis, anemia
***Normal bands (immature WBCs) = 0 to 10%

Diagnostic Evaluation

Hemoglobin- anemia
***To determine, examine palpebral conjunctiva
Hematocrit- anemia
Leukocytes
o increased in lymphomas
o decreased in leukemia
o ***Normal= 4.5-11000 /cumm
Platelets
o increased in CML, Hodgskins
o decreased in ALL, AML, bone marrow suppression
Blood or serum
o Acid phosphatase
N: 0.11-0.6 mU/ml
Inc in metastatic prostate cancer
o Alkaline phosphatase
N: 20-90 mU/ml
Inc in bone metastasis, liver CA, lymphoma
o Calcitonin- increased in medullary thyroid cancer
o Calcium N: 9-11 mg/dl in in bonne CA
o LDH N: 100-190 mU/ml inc in liver CA, lymphoma, acute leukemia
o SGOT (AST) N 5-35 mU/ml inc in liver CA
o SGPT (ALT) N: 7-40 mU/ml
o Uric acid N: 1.5-8 mg/dl
Inc in leukemia, multiple myeloma; dec in hodgskins ds, lung ca

Tumor Markers

Alpha fetoprotein (AFP) N <10 ng/ml inc in lung, pancreatic, colon, gastric,
choriocarcinoma
CA 125 N < 35 units inc in ovarian and pancreatic ca

Cellular Aberration
Carcinoembryonic antigen (CEA) N: 0-2.5 ng/ml for non-smokers; <3 ng/ml for smokers;
inc in colorectal, breast lung, stomach ca
Prostate specific antigen N 0-4 ng/ml inc in prostate CA
CA 19-9 inc in pancreatic, colon, gastric CA
CA 15-3 inc in breast CA
Estrogen receptors inc in breast CA
Human chorionic gonadotropin N 0-5 IU/L inc in choriocarcinoma

Grading

Histologic analysis of the appearance of the cells and the degree of differentiation
o ***Neoplasm- new tumor growth
Grade I cells differ slightly from normal cells and well differentiated
Grade II more abnormal cells, moderately differentiated
Grade III very abnormal cells, poorly differentiated
Grade IV immature cells, primitive, undifferentiated

Staging- the extent of the disease

O cancer in situ
I tumor limited to the tissue of origin
II limited local spread
III extensive local and regional spread
IV metastasis

TNM Classification

Describes the anatomic extent of the cancer

T- tumor size
N- degree of regional spread to the lymph nodes
M- metastasis

Choice of treatment depends on:

Type of tumor (Histological analysis; grading)

Extent of disease- (TNM, staging)
Clients physical status
Clients wishes
Combined modality therapy is more effective in destroying cancer cells.

Treatment Modalities

Surgery
Radiation
Chemotherapy
Immunotherapy

Cellular Aberration

Surgery therapy

Diagnostic
o Obtain tissue for microscopic identification of malignant cells
o Cytology specimens- cells shed from the tumors surface- aspirate, brushings
o Needle biopsy
o Incisional biopsy
***Small piece of tissue is removed
o Excisional biopsy small tumors (2-3 cm)
***The whole tumor is removed
Curative surgery in 55% of the clients
Palliative therapy
o Reduce pain
o Relieve obstruction
o Prevent hemorrhage
o Remove infecting and ulcerating tumors
o Drain abscesses

Preventive Surgery

Subtotal colectomies in clients with ulcerative colitis to prevent colon CA

Radiation Therapy

Primary modality
Local cure in early stage of Hodgkins ds, skin ca, cervical ca
Adjuvant- either preoperatively or postoperatively (colorectal, early breast ca)
Palliative- to relieve pain caused by obstruction, pathologic function, spinal cord
compression and metastasis

Radiation therapy uses high energy ionizing radiation

o Destroy the cells ability to reproduce by damaging its DNA, delaying mitosis to
repair DNA or inducing apoptosis
o Cells are most vulnerable during the DNA synthesis and mitosis (***S phase and M
phase)
o Rapidly dividing cells are most sensitive e.g. bone marrow, lymphatic tissue, GIT,
hair cells and gonads

Chain of reactions occur in the ECF resulting to the formation of free radicals that interact
readily with nearby molecules causing cellular damage
Well oxygenated tumors show a much greater response to radiation

Types of Radiation Therapy

External RT- used outside of the body
o Teletherapy- radiation delivered from a source at some distance from the target
site
o Administered by high energy x-ray machines or machines containing radioisotope
(cobalt 60)
o With skin sparing effect

Cellular Aberration
Internal RT radioisotopes directly placed into or near the tumor or into the systemic
circulation
o Brachytherapy
o Sealed source- enclosed in a sealed container e.g. cesium 137
o Intracavity- into a body cavity (24-72 hrs) e.g. radium 226
o Interstitial- in needles, beads, seeds, ribbons or catheters implanted into the tumor
e.g. gold 198, iodine 125
Unsealed RT- administered IV, into body cavity, or orally

Radiation Dose

Dependent on the sensitivity of target tissues

Tumor dose that will eradicate 95% of the tumor yet preserve normal tissues (lethal dose)
Delivered over several weeks
o For healthy tissues to repair
o When cells are actively D
o

Toxicity to Radiation Therapy

Localized
Increased if with concomitant chemotherapy
When cellular death exceeds cellular regeneration
On rapidly dividing cells
Common- alopecia, erythema, desquamation, stomatitis, xerostomia, loss of taste,
decreased salivation
Anemia, leukopenia, thrombocytopenia

Nursing Mgt in RT

Explanation about procedure- delivery, equipment, duration, positioning, sensations,

radiation precautions
Protect skin oral mucosa
o No lotion, ointments or powder on area
o Gentle oral hygiene

Key Concepts in RT

Different areas of the body are affected differently

Only the area in the treatment field is affected
Radiation dose is prescribed in units called grays (Gy)
Side effects are decreased with divided doses
Combined modality with chemotherapy and radiation has the potential for enhanced
tumor destruction as well as enhance side effects
GIT, skin and bone marrow are at greatest risk of damage
o ***RBC has the longest lifespan (120 days) among the blood cells (i.e. leukocytes,
thrombocytes)
o e.g. N & V, anorexia
o e.g. first degree burns
RT is aimed at destroying the malignant tumor w/o harming the surrounding tissues
by:

Cellular Aberration
Fractionation
Dividing the total radiation dose into small, frequent doses
Increases the probability that tumor cells be in a vulnerable phase of the cell
cycle (***S phase and M phase)
Allow normal cells to repair themselves
Side effects do not develop until approx. 10-14 days into tx and subsides 2 or more weeks
after tx
CBC during RT
o ***Because of the risk to damage to/suppression of bone marrow
***Low RBC= low oxygenation
***Low WBC (leukopenia)= risk to infxn
***Low thrombocytes= risk for bleeding
o

Skin care of the treatment field

Keep skin dry

Do not wash the area until instructed. If permitted wash gently with mild soap and
thoroughly pat dry
Do not remove marks on skin
Avoid using powder, lotions, alcohol etc.
Wear loose fitting clothing to avoid friction
Do not apply plaster/tape
Shave with electric razor. No lotion
Protect skin from sunlight, chlorinated pools, temp. extremes
Consult for spec skin rxns

Key principles for radiation safety

The greater the distance from the radiation sources, the less the exposure dose of
ionizing rays
o ***at least 6 feet away from the source
Time is limited to 30 min of direct care per shift (8hrs)
o ***Rationale: Less exposure of the nurse to the radiation
Shielding- depends on the source of radiation (lead shielding)
o ***Technicians wear a lead apron
Maintaining maximum distance from the radioactive source and limiting duration of
exposure, nurses can safely protect themselves with or without shielding
Film badge- provides a measure of whole body exposure to radiation

Safety Standards for sealed source of internal Radioactive Implants

Pt in a private room and bath

Shields, a lead container and a long handled forceps in the clients room
If source becomes dislodged, inform radiation safety officer STAT

Safety Standards for internal unsealed source of radiation

Pt in a private room and bath

All body secretions are radioactive-all surfaces are covered with protective covering
Food served on disposable plates
Trash, linens kept inside the room until after discharged
Toilets flushed several times

Cellular Aberration
Nurses should:
To wear a new pair of booties each time anyone enters the room
Wear gloves when handling body fluids
Radiation safety officer scans the patient before discharge
Precautions for the room continues even after the discharge until radiation safety officer
has lifted restrictions

Chemotherapy
Indications of Chemotherapy

Disease is widespread
Risk for undetectable disease is high
Tumor cannot be resected and is resistant to RT

Actively dividing cells are most sensitive to CT

CT directly or indirectly disrupts reproduction of cells by altering essential biochemical
processes
Cell kill hypothesis- only a percentage of cancer cells are killed with each course of
chemotherapy
Combined CT destroy more malignant cells and produce fewer side effects. Each drug
strikes the cancer cells at a different point of the cell cycle

Cell cycle phase specific drugs

Exert effect within a specific cycle

Schedule dependent
Greatest tumor cell kill when given
o Frequent divided doses
o Continuous infusion with short cycle time
Antimetabolites (*** mostly acts on G1 Phase)
o Act in S-phase
o Interfere with DNA synthesis
o
Vinca alkaloids
o Camptothecians
Act in S phase
Cause double strand DNA damage
Vinca alkaloids (vinblastiie, vincristine)
o Act in late G2 and M phase
o Block DNA production
o Prevent cell division
o Common side effects:
MyelosuppressionAutonomic and peripheral neurotoxicity
Miscellaneous Agents
o L-asparginase, hydroxyurea, pegasparse, procarbazine, imatinib mesylate
o Act in various phases (Primarily S phase)
o Inhibit synthesis
o Common side effects:
Myelosuppression, GI, hepatotoxicity
***G0 Phase- resting phase of the cell from reproduction

Cellular Aberration

Cell Cycle non-specific drugs

Alkylating drugs: (busulfan, melphalan, carboplatin

o Break DNA helix strand
o SE: Myelosuppression, htpersensitivity, GI, renal, cutaneous, 2 nd malignancies
Antitumor antibiotics : bleomycin, doxorubicin
o ..
Hormonal therapy (Glucocorticoids,
o Alter envt and inhibit tumor growth
o Common SE: GI, gynecomastia, fluid and sodium retention, menstrual
irregularity, libido changes

Administration of Chemotherapy

Depends on the type of agent; req dose; type, location, and extent of T
Dosage is based on pts total BSA, prev response to CT,
Routes:
o IV
Peripheral access on large veins
Vascular access devices (VADS)
Implanted and external vascular access cath into a maj vein of the upper
chest
Peripheral inserted central catheter (PICC) thru cephalic or basilica vein

Regional CT
o High concentrated of drug directed to localized tumors
o Topical- applied to skin
o Intra-arterial-tumor sites received
o Intra-thecal- into the CNS thru an implanted reservoir placed in the ventricles
(Ommaya reservoir)
o Other routes- oral, SQ, IM
Adverse Reactions:
o Hypersensitivity
o
o Extravasation (***infiltration)- ***can cause tissue necrosis